Phase 3 trials of fidaxomicin for the treatment of Clostridium difficile infection (CDI)

Optimer announced the combined data from its two Phase 3 trials of fidaxomicin for the treatment of patients with Clostridium difficile infection (CDI). The two fidaxomicin clinical studies were multi-center, randomized, double-blind trials, which enrolled a total of 1,164 adult subjects. Subjects with confirmed CDI received either fidaxomicin (200mg every 12 hours) or Vancocin (vancomycin, from ViroPharma, 125mg every 6 hours), the only FDA approved product for the treatment of CDI. The primary endpoint was non-inferiority compared to Vancocin in clinical cure (defined as patients requiring no further CDI therapy two days after completion of study medication). If cured, subjects were monitored for a subsequent four-week period to evaluate recurrence, which was a secondary endpoint. Global cure, also a secondary endpoint, was defined as patients who were cured and did not have a recurrence during this subsequent four-week period. In both of these studies, fidaxomicin achieved its primary endpoint of non-inferiority compared to Vancocin. More specifically, the recurrence rates were 13% for the fidaxomicin arm compared to 24% for the vancomycin arm (p < 0.001). Global cure rates were 75% for fidaxomicin compared to 63% for vancomycin (p < 0.001). Cure rates were similar for both fidaxomicin and vancomycin (88% vs. 86%).

Fidaxomicin is the first in a new class of antibiotics called macrocycles, which inhibit the bacterial enzyme RNA polymerase, resulting in rapid killing of C. difficile. The narrow-spectrum profile of fidaxomicin eradicates C. difficile selectively with minimal disruption to the normal intestinal flora, while the alternative antibiotics used to treat CDI, metronidazole and vancomycin, seriously disrupt the flora. Fidaxomicin facilitates the early return of normal physiological conditions in the colon which may be responsible for reducing CDI recurrence.